IP Library Granted Patent US 9,441,253
Granted Patent B2
US 9,441,253 · App. 14/176,008 · Granted Sep 13, 2016

Metabolic transistor in bacteria

Inventors: Ka-Yiu San (Houston, TX); George N. Bennett (Houston, TX); Hui Wu (Houston, TX)
Assignee: William Marsh Rice University
C12P13/225C12N9/001C12N9/0008C12N9/0073C12N9/1085C12N9/80C12N9/88C12N9/93C12N15/52C12P1/04C12P7/065C12P7/18C12P7/40C12P7/46C12P7/54C12P7/56C12P13/04C12P13/06C12P13/08C12P13/14C12P13/18C12P13/222C12Y102/01025C12Y102/04004C12Y102/07007C12Y103/01076C12Y103/05005C12Y114/13027C12Y205/01001C12Y205/01032C12Y205/01093C12Y305/01022C12Y305/99002C12Y401/01024C12Y602/01011Y02E50/17Y02P20/52
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Quick Facts
Patent No.
US 9,441,253
App. No.
14/176,008
Granted
Sep 13, 2016
Kind
B2
Abstract

The disclosure relates to a metabolic transistor in bacteria where a competitive pathway is introduced to compete with a product pathway for available carbon so as to control the carbon flux in the bacteria.

Claims (69)

1. A method of increasing the production of a product in a bacteria, said method comprising:

a) providing a bacteria having a product pathway producing a product, wherein a competitive pathway competes with said product pathway for available carbon, said competitive pathway requiring a cofactor that is not rate limiting;

b) introducing one or more diverting gene(s) under the control of a promoter into said bacteria to directly or indirectly divert said cofactor or an intermediate in the formation of the cofactor away from said competitive pathway;

c) allowing expression of said diverting gene(s) and reducing levels of said cofactor, and thus reducing levels of said competitive pathway;

d) thereby increasing said product pathway and said product;

wherein said cofactor and said one or more diverting genes and said products are selected from the group consisting of:

Cofactor:

Diverting gene(s) encoding:

Product:

ubiquinone

geranylgeranyl diphosphate

Fermentative products or

synthase and phytoene

lactate or acetate ethanol or

synthase and phytoene

formate, or acetate or

desaturase

succinate or 2,3 butane diol

ubiquinone

geranyl diphosphate: 4-

Fermentative products or

hydroxybenzoate

lactate or acetate ethanol or

geranyltransferase

formate, or acetate or

succinate or 2,3 butane diol

biotin

Biotin-CoA ligase or biotin

Glutamate or lysine

CoA synthetase

pantothenate

pantothenate hydrolyase

Valine

thiamine

thiamine pyridinylase or

Fermentative products or

aminopyrimidine

lactate or ethanol or formate,

aminohydrolase

or acetate or succinate or 2,3

butane diol pr

Folate or 4-

4-aminobenzoate 1-

Serine

amino-

monooxygenase or

benzoate

aminobenzoate

decarboxylase

Heme

Siroheme synthase

Fermentative products or

lactate or acetate ethanol or

formate or acetate or succinate

or 2,3 butane diol

3-Methyl-2-

2-oxoisovalerate

PHE or TYR.

oxobutanoic

dehydrogenase or 3-methyl-

acid

2-oxobutanoate

dehydrogenase

2. The method of claim 1 , wherein said promoter is a constitutive promoter.

3. The method of claim 1 , wherein said promoter is an inducible promoter.

4. The method of claim 1 , wherein said bacteria is E. coli or Corynebacterium glutamicum.

5. The method of claim 1 , wherein said cofactor is ubiquinone and said diverting gene(s) is i) crtE, crtB and crtI or ii) PGT-1.

6. The method of claim 1 , wherein said cofactor is heme and said diverting gene(s) encodes siroheme synthase.

7. The method of claim 1 , wherein said cofactor is thiamine and said diverting gene(s) encodes thiamine pyridinylase or aminopyrimidine aminohydrolase.

Assignments (2)
CONFIRMATORY LICENSE Recorded Feb 26, 2014
From: RICE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 032298/0632 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 11, 2014
From: SAN, KA-YIU; BENNETT, GEORGE N; WU, HUI
To: WILLIAM MARSH RICE UNVERSITY
Reel/Frame 032190/0011 →
Continuity (2)
Provisional Application 61763019 · Feb 11, 2013
Related Publication 20140227745A1 · Aug 14, 2014